The purpose of this research will be to examine the effects of oxygen toxicity on cultured rabbit, rat, guinea pig, and human alveolar macrophages. We will determine the length of time of exposure to 95-100 percent 02 which causes death, or membrane or enzyme damage, and will examine oxygen effects on phagocytosis of alveolar macrophages. Cell- free extracts of lung fluid will be added to cultures and examined for inhibition or acceleration of the effects of oxygen. Attempts will be made to further isolate and characterize any inhibitors or stimulators of the effects. We will attempt to produce oxygen-tolerant cells by exposure to lower concentrations of oxygen (i.e., 80-85 percent). The relationship of superoxide dismutase to tolerance of these cells and to oxygen resistance of normal cells will be examined. Gluthathione reductase and peroxidase levels will be examined in macrophages in normal and in any tolerant cells to see if these enzymes are involved in macrophage defenses. The oxygen defenses in normal alveolar macrophages will be compared to those in which phagocytosis may be producing oxidant stress in order to see if the activation of oxygen defenses interferes with bacteriocidal efficiency of macrophages.